1. Field of the Invention
Embodiments of the invention relate to stabilized compositions containing tocotrienols. In particular, compositions are stabilized by use of a metallo-protein such as lactoferrin, transferrin, ovotransferrin, ceruloplasmin, metallo-thionein and metallo-protein complexes. The compositions are useful to treat conditions such as hyperlipidemia, hypercholesteremia, atherosclerosis, diabetes and neurodegenerative diseases.
2. Description of the Related Art
Vitamin E is one of the most important phytonutrients in edible oils. There are eight naturally occurring vitamers (substances having similar vitamin activity) of vitamin E. They consist of tocopherols and tocotrienols, structurally similar molecules containing a two-ringed ‘chromanol head’ and a 16-carbon ‘phytyl tail’. In the tocopherols, the phytyl tail is saturated; in the tocotrienols it contains three double (unsaturated) bonds. All natural E vitamers are in a spatial form known as the R,R,R-stereoisomer conformation. (Theriault A, et al. Clin Biochem 32:309-319, 1999)
Tocotrienols (T3) are found primarily in the oil fraction of rice bran, palm fruit, barley, and wheat germ. Natural T3 exists in four different forms or isomers, named alpha-(5,7,8-trimethyl), beta-(5,8-dimethyl), gamma-(7,8-dimethyl) and delta-(8-monomethyl), which contain different number of methyl groups on the chromanol ring. Although all the isomers are potent free radical scavengers due to the ease of donating a hydrogen atom from the hydroxyl group on the chromanol ring, each T3 form exhibits a distinct biological activity. (Tan B. J Am Nutr Assoc 8:35-42, 2005)
T3 concentrates and isomers can be obtained through purification processes from several natural sources such as palm olein and rice bran oil. These T3 isolation procedures are intricate and difficult to do on a large scale. The Malaysian Palm Oil Board (MPOB) spearheaded extensive research and development in oil palm cultivation and revolutionized the global production of palm oil T3 and T3 derivatives for food and pharmaceutical applications.
U.S. Pat. No. 6,838,104 teaches a process to recover high yields of T3 compounds from biological sources such as palm oil, cereals, grains, and grain oils. U.S. Pat. No. 6,395,915 describes a large-scale process to isolate T3 isomers from tocopherols using reverse phase partition liquid chromatography. U.S. Pat. No. 6,224,717 describes a method for separating T3 from tocol admixtures. U.S. Pat. No. 5,670,668 discloses isolation and purification of D-gamma-T3 by crystallization and recrystallization procedures.
Several synthetic methods to derive d-T3 compounds from various organic chemicals are known in the prior art. U.S. Pat. No. 7,038,067 describes a method to synthesize D-T3 from a (2S)-vinyl-chromane compound, through hydroboration of the (2S)-vinyl-chromane to provide an organoborane, followed by coupling the organoborane with a halogenated C-14 side-chain compound under conditions of palladium-catalyzed cross-coupling. U.S. patent application No. 2005/0124687 discloses a process to derive d-T3 from a (2S) 2-hydroxymethyl-6-hydroxy-alkylchroman compound, through reaction with a farnesyl Grignard or sulfone compound.